Genetic information regarding living organisms has been recently expanding its applications in biochemistry, molecular biology, clinical medicine and other technical fields, and this trend has promoted rapid progress in the techniques for the structural analysis of DNA. A conventional method for analyzing DNA structures uses DNA microarrays, which may also be called DNA microchips. A DNA microarray consists of a slide glass or similar substrate on which DNA probes with known base sequences of different patterns are fixed. When a sample DNA as a specimen is supplied onto the substrate, the sample DNA complimentarily combines with a corresponding, specific DNA probe due to hybridization and is thereby fixed on the substrate. Accordingly, it is possible to obtain information about the base sequence of the sample DNA by locating the DNA probe which has been combined with the sample DNA.
The methods for locating a DNA probe combined with a sample DNA can be broadly divided into two types; the type that employs an optical measurement, and the type that employs an electrical measurement. In the former type of method, a sample DNA that has been fluorescently labeled is supplied onto the microarray substrate and made to combine with a DNA probe. In this state, a ray of excitation light with a predetermined wavelength is cast onto the microarray. As a result, only the DNA probe that has combined with the sample DNA produces fluorescence. Accordingly, it is possible to obtain information about the base sequence of the sample DNA by detecting the intensity of the fluorescence with a photo detector and determining which DNA probe is producing the fluorescence. This method generally requires an apparatus capable of detecting a faint fluorescence, e.g. a near-field microscope. However, some conventionally proposed apparatuses have a two-dimensional detector integrated with a DNA microarray (for example, refer to Patent Documents 1 and 2).
Integration of a DNA microarray with a detection sensor has also been attempted in the electrical measurement. One of the conventionally proposed methods uses an electrode being directly in contact with a target spot of a specimen to detect a change in its electrochemical characteristics due to hybridization. Another method uses an electrode being capacity-coupled with the target spot via an insulator film or similar device to detect a change in the electrostatic characteristics of that spot.
In the structural analysis of DNA by means of a DNA microarray, if the detection by the optical measurement and the detection by the electrical measurement can be concurrently performed, it is expected that the omission and uncertainty of the two detection methods will be compensated, so that the analytical accuracy will significantly improve. However, no conventional sensor has been capable of realizing such a hybrid analysis.
The simultaneous performance of the optical and electrical measurements is very effective not only in the analysis using a DNA microarray; it is generally effective in the observation or measurement of biological samples, such as biomedical substances. From this viewpoint, the inventors have proposed an image sensor capable of simultaneously performing an optical measurement and electrical measurement of a biological sample, as disclosed in Patent Document 3. The image sensor described in this document has a two-dimensional array of photoelectric conversion units in each of which picture elements are partially replaced by an electrode protruding upward from a protective film. This electrode is designed to some in contact with a sample placed on the protective film, thus making it possible to extract electric signals of the sample while simultaneously detecting a fluorescence or similar light emitted from the sample with the photoelectric conversion unit.
This configuration is premised on the idea that the electrical measurement is no more than a supplemental measure. Therefore, increasing the number of electrodes to enhance the spatial resolution of the two-dimensional image obtained by the electrical measurement inevitably decreases the number of photoelectric conversion units and accordingly lowers the spatial resolution of the two-dimensional image obtained by the optical measurement. Thus, the spatial resolutions of the two types of two-dimensional images cannot be simultaneously improved, so that it is difficult to always obtain results that can be complementarily used.
Patent Document 1: Japanese Unexamined Patent Application Publication No. 2002-202303
Patent Document 2: Japanese Unexamined Patent Application Publication No. 2006-4991
Patent Document 3: Japanese Unexamined Patent Application Publication No. 2005-227155